Endogenous glucocorticoids induced by a chemical stressor (ethanol) cause apoptosis in the spleen in B6C3F1 female mice.
Stress-induced increases in glucocorticoid levels can cause-apoptosis in immature thymocytes, but it is not known if glucocorticoids at these levels can also cause apoptosis in peripheral lymphocytes. In the present study, mice were exposed to ethanol (EtOH) in a model designed to represent binge drinking. This induces a substantial stress response, including an increase in corticosterone levels. Apoptosis in the spleen was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) with fluorescein-labeled dUTP. Flow cytometric analysis demonstrated a significant increase in the percentage of apoptotic cells in the spleen 2-6 h after administration of EtOH (3-6% apoptotic cells in treated mice vs 0.2-2% in controls). This increase was blocked by the glucocorticoid antagonist, RU 486, and administration of exogenous corticosterone in a manner that produced similar blood levels and kinetics as noted in EtOH-treated mice produced similar levels of apoptosis. Fluorescein-labeled Annexin V was used to confirm increased numbers of apoptotic cells in the spleen in EtOH-treated mice. These results indicate that stress-induced glucocorticoids are sufficient to induce apoptosis in the spleen, and this may be one mechanism by which stress responses cause immunosuppression.
Collier
S D
SD
Department of Biological Sciences, Mississippi State University, Mississippi State 39762, USA.
Wu
W J
WJ
Pruett
S B
SB
D000284:Administration, Oral; D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis; D002452:Cell Count / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005434:Flow Cytometry; D006727:Hormone Antagonists / Q000494:pharmacology; D007279:Injections, Subcutaneous; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000378:metabolism / Q000473:pathology*
D017304:Annexin A5; D002492:Central Nervous System Depressants; D006727:Hormone Antagonists; D015735:Mifepristone; D000431:Ethanol; D003345:Corticosterone